title: Differentiated thyroid cancer: a new perspective with radiolabeled somatostatin analogues for imaging and treatment of patients.
abstract: BACKGROUND
  The expression of somatostatin receptors (SSTR) in thyroid cells may offer the possibility to identify metastatic lesions and to select patients for peptide receptor radionuclide therapy (PRRT). We investigated (68)Ga-DOTATOC positron emission tomography/computed tomography (PET/CT) to select patients with progressive differentiated thyroid cancer (DTC) for PRRT as well as treatment response and toxicity in treated patients.
  
  
  METHODS
  We enrolled 41 patients with progressive radioiodine-negative DTC (24 women and 17 men; mean age=54.3 years, median=59 years, range=19-78 years). In all patients, [(18)F]FDG-PET/CT was performed to determine recurrent disease with enhanced glucose metabolism, and (68)Ga-DOTATOC PET/CT was used to identify SSTR expression. Dosimetric evaluation was performed with (111)In-DOTATOC scintigraphy. Eleven patients were treated with PRRT receiving a fractionated injection of 1.5-3.7 GBq (90)Y-DOTATOC/administration. Serial (68)Ga-DOTATOC PET/CT scans were performed in all treated patients to evaluate treatment response. Parameters provided by (68)Ga-DOTATOC PET/CT were analyzed as potential therapeutic predictors to differentiate responding from nonresponding. In all treated patients, adverse events and toxicity were recorded.
  
  
  RESULTS
  (68)Ga-DOTATOC PET/CT were positive in 24/41 of radioiodine-negative DTC patients. Based on the high expression of SSTR detected by (68)Ga-DOTATOC PET/CT, 13 patients were suitable for PRRT. Two out of 13 patients were not treated due to the lack of fulfillment of other study inclusion criteria. PRRT induced disease control in 7/11 patients (two partial response and five stabilization) with a duration of response of 3.5-11.5 months. Objective response was associated with symptoms relief. Functional volume (FV) over time obtained by PET/CT was the only parameter demonstrating a significant difference between lesions responding and nonresponding to PRRT (p=0.001). Main PRRT adverse events were nausea, asthenia, and transient hematologic toxicity. One patient experienced permanent renal toxicity.
  
  
  CONCLUSIONS
  In our series, SSTR imaging provided positive results in more than half of the cases with radioiodine-negative DTC, and about one third of patients were eligible for PRRT. (68)Ga-DOTATOC PET/CT seems a reliable tool both for patient selection and evaluation of treatment response. In our experience, FV determination over time seems to represent a reliable parameter to determine tumor response to PRRT, although further investigations are needed to better define its role.
authors.affiliation: 1 Nuclear Medicine, Arcispedale Santa Maria Nuova, Clinical Cancer Research Institute (IRCCS) , Reggio Emilia, Italy .
authors.forename: Annibale
authors.initials: A
authors.lastname: Versari
authors.forename: Martina
authors.initials: M
authors.lastname: Sollini
authors.forename: Andrea
authors.initials: A
authors.lastname: Frasoldati
authors.forename: Alessandro
authors.initials: A
authors.lastname: Fraternali
authors.forename: Angelina
authors.initials: A
authors.lastname: Filice
authors.forename: Armando
authors.initials: A
authors.lastname: Froio
authors.forename: Mattia
authors.initials: M
authors.lastname: Asti
authors.forename: Federica
authors.initials: F
authors.lastname: Fioroni
authors.forename: Nadia
authors.initials: N
authors.lastname: Cremonini
authors.forename: Daniel
authors.initials: D
authors.lastname: Putzer
authors.forename: Paola Anna
authors.initials: PA
authors.lastname: Erba
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000031:analogs & derivatives / Q000627:therapeutic use; D009942:Organometallic Compounds; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D017481:Receptors, Somatostatin / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000532:radiotherapy*; D014055:Tomography, Emission-Computed; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C507387:111In-DOTA-TOC; C499142:Ga(III)-DOTATOC; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; D019788:Fluorodeoxyglucose F18; D013004:Somatostatin; C496730:90Y-octreotide, DOTA-Tyr(3)-; D015282:Octreotide